The neurological phenotype

KATP channels are expressed in the brain, nerve and muscle as well as the pancreas.

Around 20% of patients with KATP channel neonatal diabetes have neurological features. This can range from mild developmental delay to DEND syndrome (developmental delay, epilepsy and neonatal diabetes). Neurodevelopmental problems may manifest as autism (comprising impaired language and social interaction and restricted/repetitive behaviours) or Attention Deficit Hyperactivity Disorder, which can impact significantly on the lives of affected patients and their families. Even patients without an overt neurological phenotype have recently been shown to have attention deficits and developmental coordination disorder on neuropsychological testing.

Early diagnosis in these cases and treatment with the sulphonylurea glibenclamide from the outset is important. Glibenclamide crosses the blood / brain barrier and may aid neurological function in patients with KATP channel neonatal diabetes. One study showed an inverse correlation between age of initiation of treatment and performance in a visuomotor task in 8 patients with the specific V59M mutation in the KCNJ11 gene. Those patients with potassium channel neonatal diabetes and developmental delay may also be helped by having a higher dose of sulphonylurea. Our clinical experience with patients also suggests that earlier treatment with glibenclamide, in the first few months of life, results in less severe neurological features, which may be due to early brain plasticity. However high doses of glibenclamide can be beneficial even in older children and many families have reported improvements in concentration and speech after the glibenclamide dose is increased. More research studies are needed to investigate this further.